LRP12

Summary

LRP12 (LDL receptor related protein 12, HGNC:31708) is a protein-coding gene on chromosome 8q22.3, encoding Low-density lipoprotein receptor-related protein 12 (Q9Y561). Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction.

This gene encodes a member of the low-density lipoprotein receptor related protein family. The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 29967 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculopharyngodistal myopathy 1 (Strong, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 130 total — 1 pathogenic
• Phenotypes (HPO): 85
• MANE Select transcript: NM_013437

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31708
Approved symbol	LRP12
Name	LDL receptor related protein 12
Location	8q22.3
Locus type	gene with protein product
Status	Approved
Aliases	ST7, FLJ12929
Ensembl gene	ENSG00000147650
Ensembl biotype	protein_coding
OMIM	618299
Entrez	29967

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000276654, ENST00000424843, ENST00000518375, ENST00000519675, ENST00000520770, ENST00000522046, ENST00000523007

RefSeq mRNA: 2 — MANE Select: NM_013437 NM_001135703, NM_013437

CCDS: CCDS47907, CCDS6303

Canonical transcript exons

ENST00000276654 — 7 exons

Exon	Start	End
ENSE00000981074	104531907	104531963
ENSE00000981078	104496972	104498076
ENSE00000981079	104495077	104495209
ENSE00002106342	104489236	104491539
ENSE00002115998	104588819	104589258
ENSE00003548988	104508939	104509074
ENSE00003680845	104499317	104499519

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 92.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4874 / max 110.7990, expressed in 1672 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
94347	4.3792	1482
94346	3.7223	1376
94345	2.3859	1015

Top tissues by expression

283 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	92.40	gold quality
cortical plate	UBERON:0005343	92.15	gold quality
ganglionic eminence	UBERON:0004023	89.34	gold quality
smooth muscle tissue	UBERON:0001135	85.78	gold quality
cartilage tissue	UBERON:0002418	85.09	gold quality
islet of Langerhans	UBERON:0000006	84.76	gold quality
ventricular zone	UBERON:0003053	84.46	gold quality
colonic epithelium	UBERON:0000397	84.24	gold quality
adrenal tissue	UBERON:0018303	84.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.63	gold quality
embryo	UBERON:0000922	82.13	gold quality
heart right ventricle	UBERON:0002080	81.46	gold quality
prefrontal cortex	UBERON:0000451	81.18	gold quality
gastrocnemius	UBERON:0001388	80.56	gold quality
body of uterus	UBERON:0009853	80.50	gold quality
muscle of leg	UBERON:0001383	80.49	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.31	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.19	gold quality
heart left ventricle	UBERON:0002084	79.95	gold quality
cardiac ventricle	UBERON:0002082	79.80	gold quality
gall bladder	UBERON:0002110	79.68	gold quality
right atrium auricular region	UBERON:0006631	79.04	gold quality
heart	UBERON:0000948	78.90	gold quality
popliteal artery	UBERON:0002250	78.87	gold quality
tibial artery	UBERON:0007610	78.87	gold quality
nucleus accumbens	UBERON:0001882	78.20	gold quality
aorta	UBERON:0000947	77.95	gold quality
cardiac atrium	UBERON:0002081	77.95	gold quality
right coronary artery	UBERON:0001625	77.73	gold quality
calcaneal tendon	UBERON:0003701	77.48	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.38
E-HCAD-5	no	2.19

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

120 targeting LRP12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-454-3P	99.91	74.01	1925

Literature-anchored findings (GeneRIF, showing 9)

• ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways. (PMID:12809483)
• As the preplate separates, Lrp12/Mig13a-positive neurons polarize in the radial plane and form a pseudocolumnar pattern, prior to moving to a deeper position within the emerging subplate layer. (PMID:20439316)
• Results indicate that low-density lipoprotein receptor-related protein 12 silencing during brain development results in cortical dyslamination and seizure sensitization. (PMID:26639854)
• Accumulation of functional promoter-associated allelic variants with impact on the transcriptional regulation of LRP12 provides a new pathomechanism for GGs, i.e. highly differentiated epileptogenic brain tumors (PMID:27142828)
• LRP12 DNA methylation as a powerful predictive marker for carboplatin resistance. (PMID:30029672)
• GGC repeat expansions in LRP12 gene is associated with oculopharyngodistal myopathy. (PMID:31332380)
• Oculopharyngodistal myopathy with coexisting histology of systemic neuronal intranuclear inclusion disease: Clinicopathologic features of an autopsied patient harboring CGG repeat expansions in LRP12. (PMID:32493488)
• LRP12 is an endogenous transmembrane inactivator of alpha4 integrins. (PMID:37330909)
• CGG repeat expansion in LRP12 in amyotrophic lateral sclerosis. (PMID:37339631)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrp12	ENSDARG00000098845
mus_musculus	Lrp12	ENSMUSG00000022305
rattus_norvegicus	Lrp12	ENSRNOG00000004152
drosophila_melanogaster	arr	FBGN0000119

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LDLR (ENSG00000130164), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP1B (ENSG00000168702), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Low-density lipoprotein receptor-related protein 12 — Q9Y561 (reviewed: Q9Y561)

Alternative names: Suppressor of tumorigenicity 7 protein

All UniProt accessions (2): Q9Y561, E5RIW8

UniProt curated annotations — full annotation on UniProt →

Function. Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. May act as a tumor suppressor.

Subunit / interactions. May interact with RACK1, ZFYVE9 and NMRK2.

Subcellular location. Membrane. Coated pit.

Tissue specificity. Widely expressed in heart, skeletal muscle, brain, lung, placenta and pancreas, but not in tissues consisting of a large number of epithelial cells, such as liver and kidney. Expressed at very low levels in a number of tumor-derived cell lines.

Disease relevance. Oculopharyngodistal myopathy 1 (OPDM1) [MIM:164310] A form of oculopharyngodistal myopathy, a muscle disorder characterized by progressive ptosis, external ophthalmoplegia, and weakness of the masseter, facial, pharyngeal, and distal limb muscles. The myopathological features are presence of rimmed vacuoles in the muscle fibers and myopathic changes of differing severity. OPDM1 inheritance pattern is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. The causative mutation is a heterozygous trinucleotide repeat expansion (CGG) in the 5-prime untranslated region of the gene. The number of repeats in OPDM1 patients is usually greater than 100. Amyotrophic lateral sclerosis 28 (ALS28) [MIM:620452] A form of amyotrophic lateral sclerosis, a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. Sensory abnormalities are absent. The pathologic hallmarks of the disease include pallor of the corticospinal tract due to loss of motor neurons, presence of ubiquitin-positive inclusions within surviving motor neurons, and deposition of pathologic aggregates. The etiology of amyotrophic lateral sclerosis is likely to be multifactorial, involving both genetic and environmental factors. The disease is inherited in 5-10% of the cases. ALS28 is an autosomal dominant form characterized by adult onset of slowly progressive limb muscle weakness and atrophy resulting in gait difficulties, loss of ambulation, and distal upper limb weakness. Facial involvement is rare, but some patients may have respiratory insufficiency. The disease is caused by variants affecting the gene represented in this entry. The causative mutation is a heterozygous trinucleotide repeat expansion (CGG) in the 5-prime untranslated region of the gene. The number of repeats in ALS28 patients is between 61 and 100.

Similarity. Belongs to the LDLR family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y561-1	1	yes
Q9Y561-2	2

RefSeq proteins (2): NP_001129175, NP_038465* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000859	CUB_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR023415	LDLR_class-A_CS	Conserved_site
IPR035914	Sperma_CUB_dom_sf	Homologous_superfamily
IPR036055	LDL_receptor-like_sf	Homologous_superfamily

Pfam: PF00057, PF00431

UniProt features (44 total): disulfide bond 18, domain 7, glycosylation site 6, region of interest 4, compositionally biased region 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y561-F1	63.10	0.13

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (18): 47–76, 103–122, 166–178, 173–191, 185–200, 215–232, 222–245, 239–254, 259–285, 375–388, 382–401, 395–410, 413–426, 420–439, 433–448, 451–463, 458–476, 470–485

Glycosylation sites (6): 75, 146, 284, 366, 409, 441

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-975634	Retinoid metabolism and transport
R-HSA-1430728	Metabolism
R-HSA-196854	Metabolism of vitamins and cofactors
R-HSA-2187338	Visual phototransduction
R-HSA-6806667	Metabolism of fat-soluble vitamins
R-HSA-9709957	Sensory Perception

MSigDB gene sets: 575 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, FXR_IR1_Q6, XU_HGF_TARGETS_REPRESSED_BY_AKT1_UP, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, PAL_PRMT5_TARGETS_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_GROWTH, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, CTATGCA_MIR153, GOBP_LEUKOCYTE_MIGRATION, BROWNE_HCMV_INFECTION_24HR_UP, TGTGTGA_MIR377, AAAGGGA_MIR204_MIR211

GO Biological Process (10): neuron migration (GO:0001764), endocytosis (GO:0006897), cell adhesion (GO:0007155), signal transduction (GO:0007165), neuron projection development (GO:0031175), integrin activation (GO:0033622), regulation of growth (GO:0040008), lymphocyte migration into lymphoid organs (GO:0097021), vesicle-mediated transport (GO:0016192), cell migration (GO:0016477)

GO Molecular Function (3): low-density lipoprotein particle receptor activity (GO:0005041), integrin binding (GO:0005178), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), membrane (GO:0016020), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Visual phototransduction	1
Metabolism of fat-soluble vitamins	1
Metabolism	1
Sensory Perception	1
Metabolism of vitamins and cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	3
membrane	2
cellular anatomical structure	2
cell migration	1
generation of neurons	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
neuron development	1
plasma membrane bounded cell projection organization	1
protein-containing complex assembly	1
growth	1
regulation of biological process	1
lymphocyte migration	1
transport	1
cell motility	1
low-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
binding	1
cell periphery	1
endomembrane system	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRP12	NOTCH2NLA	Q7Z3S9	609
LRP12	NBPF19	A0A087WUL8	546
LRP12	GIPC1	O14908	528
LRP12	LRP11	Q86VZ4	490
LRP12	GRB2	P29354	410
LRP12	ABL1	P00519	409
LRP12	SRBD1	Q8N5C6	401
LRP12	BMP1	P13497	383
LRP12	ZFPM2	Q8WW38	377
LRP12	SYDE2	Q5VT97	372
LRP12	C1S	P09871	371
LRP12	C1R	P00736	364
LRP12	CHRM5	P08912	353
LRP12	TMEM263	Q8WUH6	348
LRP12	DHPS	P49366	336

IntAct

74 interactions, top by confidence:

A	B	Type	Score
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
KIR3DL2	METTL15	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
ZNRF4	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
MRAP2	GOLIM4	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
TMED6	SMPD2	psi-mi:“MI:0914”(association)	0.530
SCNN1D	ABHD16A	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
RACK1	LRP12	psi-mi:“MI:0915”(physical association)	0.510
LRP12	NMRK2	psi-mi:“MI:0915”(physical association)	0.510
ZFYVE9	LRP12	psi-mi:“MI:0915”(physical association)	0.510
LRP12	RACK1	psi-mi:“MI:0915”(physical association)	0.510
LRP12	ACTN2	psi-mi:“MI:0915”(physical association)	0.370
LRP12	MYOT	psi-mi:“MI:0915”(physical association)	0.370
SNAPIN	LRP12	psi-mi:“MI:0915”(physical association)	0.370
	SNAP23	psi-mi:“MI:0914”(association)	0.350
NS3	C15orf61	psi-mi:“MI:0914”(association)	0.350
rep	GPR89A	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
TTMP	TMEM223	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CTLA4	TMEM120B	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350

BioGRID (84): LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS), LRP12 (Affinity Capture-MS)

ESM2 similar proteins: A2AR95, A4IHY6, B7ZWI3, D3ZF92, O15165, O43278, O75509, O88204, P98153, P98154, Q0VBF2, Q1L8G6, Q29RU0, Q4KMG9, Q566M8, Q5DTZ6, Q5HZW5, Q5R662, Q5R8E0, Q5RD34, Q5RF74, Q5VUB5, Q61003, Q68FU0, Q6AXS2, Q6NRX0, Q6UWW9, Q6ZPS6, Q6ZUJ8, Q7TQH7, Q86YD5, Q8BGN6, Q8BLD6, Q8BUJ9, Q8R182, Q8TEB7, Q8WUU8, Q91ZV2, Q91ZV3, Q96PD2

Diamond homologs: A2AR95, A2ARV4, A4IHY6, C0HL13, E9Q6D8, G3V928, O75074, O75197, O75581, O88204, O88307, O88572, P0DSP1, P13671, P35953, P56677, P61134, P61135, P86091, P98153, P98154, P98155, P98156, P98157, P98158, P98160, P98163, P98164, P98165, P98166, P98167, Q04833, Q06561, Q07954, Q0IIH7, Q14114, Q28832, Q29RU4, Q5HZW5, Q5R662

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 109 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of membrane potential	5	12.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

130 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	107
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
692233	NM_013437.5:c.-102CGG[(90_?)]	Pathogenic

SpliceAI

1569 predictions. Top by Δscore:

Variant	Effect	Δscore
8:104495212:T:C	acceptor_gain	1.0000
8:104495218:G:GC	acceptor_gain	1.0000
8:104498091:G:GC	acceptor_gain	1.0000
8:104498101:A:C	acceptor_gain	1.0000
8:104499375:AAT:A	donor_gain	1.0000
8:104499520:C:CC	acceptor_gain	1.0000
8:104531900:GACTT:G	donor_loss	1.0000
8:104531901:ACTTA:A	donor_loss	1.0000
8:104531902:CT:C	donor_loss	1.0000
8:104531903:TT:T	donor_loss	1.0000
8:104531904:T:TG	donor_loss	1.0000
8:104531905:A:AT	donor_loss	1.0000
8:104531906:C:A	donor_loss	1.0000
8:104491539:CCTAC:C	acceptor_loss	0.9900
8:104491540:C:CA	acceptor_loss	0.9900
8:104491540:C:CC	acceptor_gain	0.9900
8:104491541:T:A	acceptor_loss	0.9900
8:104495072:TATAC:T	donor_loss	0.9900
8:104495073:ATACC:A	donor_loss	0.9900
8:104495074:TA:T	donor_loss	0.9900
8:104495075:ACCTG:A	donor_loss	0.9900
8:104495076:C:CT	donor_loss	0.9900
8:104495206:TGAT:T	acceptor_gain	0.9900
8:104495207:GAT:G	acceptor_gain	0.9900
8:104495210:C:CC	acceptor_gain	0.9900
8:104495211:T:C	acceptor_gain	0.9900
8:104495211:T:TC	acceptor_gain	0.9900
8:104495212:T:TC	acceptor_gain	0.9900
8:104495218:G:C	acceptor_gain	0.9900
8:104495222:A:AC	acceptor_gain	0.9900

AlphaMissense

5664 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:104497029:A:T	L508H	1.000
8:104497039:C:G	G505R	1.000
8:104497042:A:G	C504R	1.000
8:104497049:G:C	S501R	1.000
8:104497049:G:T	S501R	1.000
8:104497051:T:G	S501R	1.000
8:104497053:C:T	G500E	1.000
8:104497054:C:G	G500R	1.000
8:104497054:C:T	G500R	1.000
8:104497062:G:T	A497D	1.000
8:104497124:A:C	C476W	1.000
8:104497125:C:G	C476S	1.000
8:104497125:C:T	C476Y	1.000
8:104497126:A:G	C476R	1.000
8:104497126:A:T	C476S	1.000
8:104497143:C:G	C470S	1.000
8:104497144:A:T	C470S	1.000
8:104497148:C:A	W468C	1.000
8:104497148:C:G	W468C	1.000
8:104497164:C:G	C463S	1.000
8:104497165:A:G	C463R	1.000
8:104497165:A:T	C463S	1.000
8:104497178:A:C	C458W	1.000
8:104497179:C:G	C458S	1.000
8:104497179:C:T	C458Y	1.000
8:104497180:A:T	C458S	1.000
8:104497185:A:C	F456C	1.000
8:104497235:G:C	C439W	1.000
8:104497236:C:G	C439S	1.000
8:104497237:A:G	C439R	1.000

dbSNP variants (sampled 300 via entrez): RS1000006749 (8:104524612 G>A,T), RS1000010543 (8:104533328 C>G), RS1000013629 (8:104587068 A>G), RS1000043905 (8:104585269 A>G), RS1000105859 (8:104575430 G>A), RS1000160528 (8:104581341 A>G), RS1000181546 (8:104528890 T>C), RS1000219232 (8:104493797 T>C), RS1000271534 (8:104493556 T>A,G), RS1000282328 (8:104539784 A>T), RS1000289105 (8:104580837 A>G), RS1000356385 (8:104524997 G>C), RS1000377322 (8:104574567 C>G), RS1000381908 (8:104546307 G>A,C,T), RS1000417861 (8:104546065 T>C)

Disease associations

OMIM: gene MIM:618299 | disease phenotypes: MIM:164310, MIM:620452, MIM:613688

GenCC curated gene-disease

Disease	Classification	Inheritance
oculopharyngodistal myopathy 1	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
oculopharyngodistal myopathy 1	Moderate	AD

Mondo (4): oculopharyngodistal myopathy 1 (MONDO:0020793), amyotrophic lateral sclerosis 28 (MONDO:0957538), long QT syndrome 2 (MONDO:0013367), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (3): Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000183	Tongue muscle weakness
HP:0000218	High palate
HP:0000301	Abnormality of facial musculature
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000508	Ptosis
HP:0000544	External ophthalmoplegia
HP:0000590	Progressive external ophthalmoplegia
HP:0000597	Ophthalmoparesis
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001315	Reduced tendon reflexes
HP:0001324	Muscle weakness
HP:0001337	Tremor
HP:0001488	Bilateral ptosis
HP:0001604	Vocal cord paresis
HP:0001611	Hypernasal speech
HP:0001618	Dysphonia
HP:0001639	Hypertrophic cardiomyopathy
HP:0001644	Dilated cardiomyopathy
HP:0001824	Weight loss
HP:0002015	Dysphagia
HP:0002058	Myopathic facies
HP:0002091	Restrictive ventilatory defect
HP:0002098	Respiratory distress
HP:0002100	Recurrent aspiration pneumonia
HP:0002380	Fasciculations

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001155_2	Vascular endothelial growth factor levels	5.000000e-23
GCST001493_1	Glaucoma (primary open-angle)	9.000000e-10
GCST002129_15	Periodontitis (DPAL)	6.000000e-06
GCST004776_43	Systolic blood pressure	7.000000e-09
GCST004776_93	Systolic blood pressure	5.000000e-07
GCST006585_49	Blood protein levels	3.000000e-12
GCST006941_33	Irritable mood	4.000000e-08
GCST007627_4	Impulsivity (attentional)	2.000000e-06
GCST010724_16	HOMA-B (corrected for HOMA-IR)	1.000000e-07
GCST011494_41	Daytime nap	5.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0009594	irritability measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0004469	HOMA-B
EFO:0007828	daytime rest measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C563614	Long Qt Syndrome 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

42 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	decreases expression, affects cotreatment	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Estradiol	affects cotreatment, increases expression	2
Valproic Acid	decreases expression, decreases methylation, increases expression	2
Aflatoxin B1	affects expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
cinnamaldehyde	increases expression	1
sulforaphane	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
potassium chromate(VI)	decreases expression	1
nickel sulfate	decreases expression	1
1-hydroxypyrene	decreases expression	1
methacrylaldehyde	increases expression, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
entinostat	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
torcetrapib	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Acrolein	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	decreases expression	1
Arsenic	increases abundance, increases expression, affects cotreatment	1
Cadmium	increases abundance, increases expression	1
Cisplatin	increases expression	1

Clinical trials (associated diseases)

53 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT07277582	PHASE2/PHASE3	RECRUITING	Evaluation of Efficacy and Safety of THRV-1268 in Long QT Syndrome Type 2 (LQTS 2)
NCT07075445	Not specified	RECRUITING	Observational Study to Describe Health-Related Quality of Life and Measure Disease Burden Among Patients With Long QT Syndrome Types (LQTS) 2 and 3
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives